Transcutaneous immunization (TCI), the introduction of antigens using an application to intact skin, is a new technology that could decrease the complications associated with the use of needles and improve access to vaccination. We have demonstrated that application of cholera toxin (CT) to the skin induces potent immune responses without evidence of systemic toxicity. The use of CT as an adjuvant on the skin also results in classic antibody boosting kinetics, the presence of serum and mucosal antibodies to co-administered antigens and protective responses. Childhood and neonatal tetanus and diphtheria remain significant worldwide problems. The incidence of tetanus in the developing world reflects non-compliance with immunization. A simpler immunization technique using TCI could decrease the barriers to immunization and improve immunization rates. Our aim is to use a relatively simple model vaccine such as the tetanus booster to develop the fundamental principals of TCI. Optimization studies on the dose and concentration of adjuvant (CT) and antigens (TT and DT) will be conducted to maximize the immune response; challenge studies (tetanus) and neutralization assays (diphtheria) will assess the functional response to TCI. The data generated in these studies provide a rational basis for the design of clinical trials leading towards a transcutaneous tetanus booster PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE